title: Tff3, as a novel peptide, regulates hepatic glucose metabolism.
abstract: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with hepatic glucose intolerance and insulin resistance. The trefoil peptides are a family of small regulatory proteins and Tff3 is widely expressed in multiple tissues including liver. But the roles of Tff3 in regulation of glucose metabolism and insulin sensitivity in liver remain unclear. Here we show that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet-induced obese mice. Overexpression of Tff3 in primary mouse hepatocytes inhibited the expression of gluconeogenic genes, including G6pc, PEPCK and PGC-1α, subsequently decreasing cellular glucose output. GTT and ITT experiments revealed that adenovirus-mediated overexpression of Tff3 in diabetic or obese mice improved glucose tolerance and insulin sensitivity. Collectively, our results indicated that Tff3 peptides are involved in glucose homeostasis and insulin sensitivity, providing a promising peptide on new therapies against the metabolic disorders associated with T2DM.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xue
authors.forename: Lian
authors.initials: L
authors.lastname: Shen
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Huabing
authors.initials: H
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Anfang
authors.initials: A
authors.lastname: Cui
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D005943:Gluconeogenesis / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D009077:Mucins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000071165:Trefoil Factor-3
chemical_list: D017931:DNA Primers; D009077:Mucins; C493263:Tff3 protein, mouse; D000071165:Trefoil Factor-3; D005947:Glucose